Variant 6-119193769-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005907.4(MAN1A1):c.1326+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000522 in 1,590,838 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 2 hom. )

Consequence

MAN1A1
NM_005907.4 splice_region, intron

Scores

Splicing: ADA: 0.00004433

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.423

Variant links:

Genes affected

MAN1A1 (HGNC:6821): (mannosidase alpha class 1A member 1) This gene encodes a class I mammalian Golgi 1,2-mannosidase which is a type II transmembrane protein. This protein catalyzes the hydrolysis of three terminal mannose residues from peptide-bound Man(9)-GlcNAc(2) oligosaccharides and belongs to family 47 of glycosyl hydrolases. [provided by RefSeq, Jul 2012]

MAN1A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-119193769-T-C is Benign according to our data. Variant chr6-119193769-T-C is described in ClinVar as [Benign]. Clinvar id is 723483.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MAN1A1	NM_005907.4 linkuse as main transcript	c.1326+8A>G	splice_region_variant, intron_variant	ENST00000368468.4	NP_005898.2	P33908-1
MAN1A1	XM_005266986.5 linkuse as main transcript	c.1575+8A>G	splice_region_variant, intron_variant		XP_005267043.1
MAN1A1	XM_011535833.3 linkuse as main transcript	c.759+8A>G	splice_region_variant, intron_variant		XP_011534135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAN1A1	ENST00000368468.4 linkuse as main transcript	c.1326+8A>G		splice_region_variant, intron_variant		2	NM_005907.4	ENSP00000357453.3		P33908-1

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

419

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00931

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.000770

AC:

189

AN:

245486

Hom.:

AF XY:

0.000566

AC XY:

AN XY:

132512

show subpopulations

Gnomad AFR exome

AF:

0.00982

Gnomad AMR exome

AF:

0.000693

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000268

Gnomad OTH exome

AF:

0.000666

GnomAD4 exome

AF:

0.000284

AC:

408

AN:

1438510

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

173

AN XY:

716804

show subpopulations

Gnomad4 AFR exome

AF:

0.00954

Gnomad4 AMR exome

AF:

0.000823

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000355

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000549

Gnomad4 OTH exome

AF:

0.000789

GnomAD4 genome

AF:

0.00277

AC:

422

AN:

152328

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00936

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00325

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.4

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000044

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over